Oric announces initial data from ongoing ORIC-114 Phase 1 dose escalation

Oric Pharmaceuticals announced initial data from the ongoing ORIC-114 Phase 1 dose escalation trial for patients with EGFR or HER2 exon 20 mutated non-small cell lung cancer at the European Society of Medical Oncology Congress 2023. ORIC-114 is being evaluated in a Phase 1 dose escalation clinical trial in patients with advanced solid tumors with EGFR and HER2 exon 20 alterations or HER2 amplifications. Patients previously treated with an exon 20 targeted agent are eligible, including patients with CNS metastases that are either treated or untreated but asymptomatic. Nearly all other clinical studies with EGFR exon 20 inhibitors severely restricted the eligible patient population and excluded patients with active or untreated brain metastases and patients previously treated with an EGFR exon 20 inhibitor, making this data set one of the first and most comprehensive in this population. The primary objectives are to determine the recommended Phase 2 dose, and additional objectives include characterization of the safety, tolerability, pharmacokinetic, and preliminary antitumor activity. As of September 26, 2023, 50 patients received ORIC-114 and were heavily pre-treated, with exceptionally high rates of prior exon 20 targeted therapies and brain metastases at baseline. Of the 21 EGFR exon 20 insertion mutated NSCLC patients, in addition to chemotherapy. 81% were treated with greater than or equal to1 prior EGFR exon 20 targeted agent, nearly all of whom received prior amivantamab; 19% were treated with multiple prior EGFR exon 20 targeted agents; and 86% presented with CNS metastases at baseline. Of the 24 HER2 exon 20 insertion mutated NSCLC patients 30% were treated with a prior HER2 targeted agent; and 38% presented with CNS metastases at baseline. ORIC-114 demonstrated a favorable pharmacokinetic profile with dose proportional increase in exposure, low intra-cohort variability, and a half-life of ~10-15 hours, which supports QD dosing. ORIC-114 was well-tolerated with mostly Grade 1 and 2 treatment-related adverse events (TRAEs) and little evidence of off-target toxicities. Rash was limited to Grade 1 and 2 events, and there was no Grade 3 or greater treatment related rash. Diarrhea was primarily Grade 1 and 2, with only 6% of patients experiencing Grade 3 diarrhea. There were only 4% discontinuations for TRAEs. The maximum tolerated dose has not been reached.